The goal of our research has been to identify membrane antigens expressed by human monocytes, macrophages and their progenitors that relate to the differentiation and function of these cells. We have developed a panel of mouse monoclonal antibodies raised against human monocytes and myeloid leukemia cells that identify a series of seven unique surface determinants borne by human monocytes and other myeloid cells. Mo1 is a glycoprotein expressed by monocytes, granulocytic cells (from myelocyte to mature neutrophil), a subset of null cells, and histiocytic cells in spleen and lymph node. Eighty percent of patients with myelomonocytic leukemia (FAB M4, M5) demonstrate Mo1 on their leukemic cells whereas 38% of patients with acute granulocytic leukemia (M1, M2, M3) bear this marker. Antibody blocking studies suggest that Mo1 is associated with the C3bi receptor (CR III) on monocytes and granulocytes. Mo2 is a glycoprotein whose expression is selective for peripheral blood monocytes to the exclusion of other circulating elements. This relative specificity for monocytes has resulted in the use of techniques (complement lysis and cell sorting) by which monocytes can be selectively depleted or purified for studies assessing the role of these cells in various in vitro immune phenomena (antigen presentation, antibody-dependent cellular cytotoxicity and natural killing). Mo2 is borne by myeloid leukemia cells with monocytic differentiation (45% of patients with M4 and M5) with a smaller frequency (16%) on the granulocytic variants. Mo3 is an antigen that is associated with monocyte-to-macrophage differentiation, being weakly expressed by circulating monocytes but increasing in antigen density as a function of time in culture under conditions favoring macrophage transformation. Mo4 is an antigen found on both monocytes and platelets (and bone marrow megakaryocytes). Mo5 is expressed by most myeloid bone marrow precursors (from promyelocyte to band) as well as circulating monocytes and granulocytes. Leukemic cells from 30% of patients with granulocytic leukemia bear Mo5 whereas 54% of patients with myelomonocytic leukemia are Mo5+. Mo5 has reversible modulation on the monocyte membrane after exposure to anti-Mo5 monoclonal antibody. Mo6 is a glycoprotein whose pattern of expression is similar to that of Mo5. Plt-1 is an antigen specific for platelets and bone marrow megakaryocytes. Isolated patients with CML in blast crisis bear Plt-1 on their leukemic cells, suggesting the diagnosis of megakaryocytic leukemia.